In objective (A) Li-Fraumeni breast epithelial cells which spontaneously immortalize are used to to evaluate the efficacy of chemopreventive agents to inhibit the spontaneous immortalization of these cells, including their effect on relevant markers during the process of immortalization. In objective (B) Potential screen systems for chemopreventive agents are established that are based on hTERT-immortalized skin fibroblasts from patients with dominantly heritable cancer syndromes. These cells are further transduced with known genetic elements which are involved in cancer progression. The effects of chemopreventive agents on these cells are determined.